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PAH is a severe, progressive disease1

Pulmonary arterial hypertension (PAH) results from restricted flow through the pulmonary arteries, leading to increased pulmonary vascular resistance (PVR) and, ultimately, right heart failure and death.2

Hemodynamic trends in pulmonary arterial pressure (PAP), PVR, and cardiac output (CO) correlate with increasing disease severity.3 Early in the disease, PVR and PAP may be elevated, but due in part to right ventricular (RV) compensation, CO remains within normal range for an indeterminate time. Patients may not be diagnosed until they present with overt symptoms such as dyspnea, fatigue, and edema in the lower extremities.4

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Risk assessment

PAH is associated with diverse pathologic events

Hypertrophy diagram
Pulmonary vasoconstriction

The pulmonary arteries contract, and vascular resistance increases.3,4

Right ventricular strain and dysfunction diagram
Right ventricular strain and dysfunction

Chronic elevated pressures lead to right ventricular strain and overload.3,5

Fibrosis diagram
Fibrosis

Over time, the vascular intima thickens, further impeding blood flow.5

Hypertrophy diagram
Hypertrophy

Vascular hypertrophy occurs in the presence of developing lesions and other arterial abnormalities.5,6

In situ thrombosis diagram
In situ thrombosis

Abnormalities in platelet activation and function promote thrombosis and can lead to increased vasoconstriction.6

A system out of balance

Endothelial dysfunction results in overproduction of vasoconstrictors such as endothelin-1 (ET-1) and underproduction of vasodilators such as nitric oxide and prostacyclin.4,5

ET-1 and its receptors (ETA and ETB) mediate a variety of deleterious effects such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation.7

Because 3 separate signaling pathways are involved in PAH, the use of combination therapy is a recommended treatment strategy.2

Pathways of PAH

OPSUMIT® (macitentan) acts on the endothelin pathway, 1 of 3 principal pathways in PAH7,8

Pathway Drug Class
Endothelin Endothelin receptor antagonists
Prostacyclin Prostanoids
Nitric oxide PDE-5 inhibitors, sGCs
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Risk assessment

Learn more about OPSUMIT® clinical data

View Overall SERAPHIN Results

SERAPHIN PAH-related hospitalization results

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View SERAPHIN PAH-CTD subgroup data

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PDE-5=phosphodiesterase type 5; sGCs=soluble guanylate cyclase stimulator.
References: 1. McLaughlin V, Shah S, Souza R, Humbert M. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015;65:1976–1997. 2. Humbert M, Kovacs G, Hoeper MM, et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Heart J. 2022;43(38):3618-3731. 3. Howard LS. Prognostic factors in pulmonary arterial hypertension: assessing the course of the disease. Eur Respir Rev. 2011;20(122):236-242. 4. Minai OA, Budev MM. Diagnostic strategies for suspected pulmonary arterial hypertension: a primer for the internist. Cleve Clin J Med. 2007;74:737-747. 5. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension. J Am Coll Cardiol. 2009;53(17):1573-1619. 6. Blaise G, Langleben D, Hubert B. Pulmonary arterial hypertension: pathophysiology and anesthetic approach. Anesthesiology. 2003;99(6):1415-1432. 7. Rich S. Pulmonary hypertension. In: Bonow RO, Mann DL, Zipes DE, Libby P, eds. Braunwald’s Heart Disease. A Textbook of Cardiovascular Disease. Vol 2. 9th ed. Saunders Elsevier; 2012:1696-1718. 8. OPSUMIT® [prescribing information]. Actelion Pharmaceuticals US, Inc.

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